肝癌是世界上死亡率非常高的惡性腫瘤，特色是具有高度異質性以及復發率。中心體相關蛋白CPAP (centrosomal P4.1 associated protein) 在先前的研究中發現會在肝癌患者高度表達，並且會促進肝癌的發展。腫瘤微環境，包含免疫細胞以及各種細胞因子，參與在各種腫瘤的進展中，腫瘤微環境中的巨噬細胞稱為腫瘤相關巨噬細胞，根據先前研究指出，腫瘤會透過CD24蛋白與腫瘤相關巨噬細胞的Siglec-10蛋白結合，進而誘發巨噬細胞「不要吃我」的訊號，導致吞噬作用被抑制，進而躲過免疫反應。本論文研究發現，在肝癌細胞Hep3B中過度表達CPAP，其會透過IL-6/STAT3訊息傳遞途徑增加CD24的表達。當加入了STAT3抑制劑，會抑制CPAP所增加的CD24表現。本研究利用THP-1細胞所分化成的巨噬細胞進行吞噬作用實驗，證實在過度表現CPAP的肝癌細胞較不會被吞噬作用殺死；若是利用siRNA技術將大量表現CPAP的肝癌細胞中的CD24表現敲低，則大大增加了肝癌細胞被巨噬細胞所吞噬。有趣的是，使用CPAP大量表現之肝癌細胞株的條件培養基，與M0巨噬細胞進行共培養後，分化成為腫瘤相關巨噬細胞，則發現其吞噬作用能力被大大削弱了。本研究成果證實在肝癌細胞中CPAP可以透過STAT3來增加CD24表現，進而達到抑制腫瘤巨噬細胞的吞噬作用。

Hepatocellular carcinoma (HCC) is the sixth most common cancer in the world. The tumor microenvironment (TME) is a popular target for cancer treatment, and tumor-associated macrophages (TAM) are abundant in TME. Our previous studies indicated that CPAP is overexpressed in liver cancer. In this study, we found that CPAP can increase the expression of CD24 via the IL-6/STAT3 pathway. When HCC cells were treated with STAT3 inhibitor, the CPAP-enhanced CD24 expression was significantly decreased. The results of the phagocytosis assay further showed that overexpression of CPAP in HCC cells reduces the phagocytic activity of THP-1 cell-derived macrophages. Knocked-down CD24 increases macrophage clearance ability in CPAP-overexpressing HCC cells. Our results support that the position CPAP plays an important role in regulating macrophage phagocytotic ability in HCC.

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